20 results about "Hla molecules" patented technology

The present invention discloses a method for predicting peptides that are capable of binding to HLA molecules that incorporate the crystal structure of HLA molecules. An improved HLA-specific peptide docking workflow is used to simulate the occupancy of a peptide on the binding pocket of an HLA molecule, and three models are trained to predict the binding of the peptide to HLA molecules. The results show that these models predict HLA-allele specific binding peptides with extremely high accuracy.

This disclosure provides compositions and methods of making cells, such as allogenic cells, engineered to evade host immune responses, particularly from T cells and natural killer cells, and populations thereof. The compositions and methods for making engineered cells include making genetic modifications that reduce or eliminate the expression of an NKG2D ligand or integrate sequences encoding HLA molecules, such as HLA-E or HLA-G. Such modifications can enhance the survival of the engineered cells within a host without impeding their ability to differentiate into functional cell types, such as cardiomyocytes.

The invention relates to the technical field of tumor immunotherapy, in particular to an HLA restrictive neoantigen polypeptide based on malignant ascites tumor cells and application of the HLA restrictive neoantigen polypeptide. The invention provides cholangiocarcinoma neoantigen polypeptide. The amino acid sequence of the neoantigen polypeptide is shown as SEQ ID NO.1, 2 or 3. The tumor neoantigen polypeptide is separated and screened from malignant ascites of a biliary duct cancer patient, has high affinity with HLA molecules, can stimulate generation of tumor specific T cells, further generates immune response of targeted tumor cells, can be used as a target spot for clinical treatment or diagnosis of tumors, and has good application prospects. Good application prospects are realized in tumor immunotherapy.

To provide antigen-specific T cell receptors and chimeric antigen receptors, and methods of use in immune signaling modulation for cancer immunotherapy.SOLUTION: The present invention relates to T cell receptors (TCRs) against cancer / testis antigens NY-ESO-1 and CT83 presented by multiple HLA molecules. Preferred TCRs of the invention derived from human T cells exhibit high affinity and antigen specificity in vitro and in vivo. The present invention also relates to modulation of TCR-T CAR-T cell signaling and functional persistence in cancer immunotherapy. In one aspect, the disclosure relates to methods for identifying and functionally validating TCRs from cancer antigen-specific T cells.SELECTED DRAWING: None

The invention relates to the technical field of tumor immunotherapy, in particular to an HLA-A * 11: 01 restrictive neoantigen peptide based on malignant pleural effusion tumor cells and application of the HLA-A * 11: 01 restrictive neoantigen peptide. The tumor neoantigen polypeptide is separated and screened from malignant pleural effusion of a lung cancer patient, and the amino acid sequence of the neoantigen polypeptide is shown as any one of SEQ ID NO.1-9. The tumor neoantigen polypeptide has high affinity with HLA molecules, can stimulate generation of tumor specific T cells, and can be used as a target spot for clinical treatment or diagnosis of tumors. The invention also provides a method for separating and screening the tumor neoantigen polypeptide, the method solves the problem that the neoantigen of a non-surgical treatment patient cannot be obtained, and an effective method is provided for the development of the tumor neoantigen polypeptide.

This invention relates to T-cell receptors (TCRs) targeting the cancer / testis antigens NY-ESO-1 and CT83 presented by various HLA molecules. Preferred TCRs of this invention are derived from human T cells and exhibit high affinity and high antigen specificity both in vitro and in vivo. Furthermore, this invention also relates to the regulation of TCR-T and CAR-T cell signaling and their functional persistence in cancer immunotherapy.

The invention relates to the technical field of tumor immunotherapy, in particular to tumor neoantigen polypeptide and a separation and screening method thereof. The amino acid sequence of the tumor neoantigen polypeptide provided by the invention is shown as SEQ ID NO.1, 2, 3 or 4. The tumor neoantigen polypeptide has high affinity with HLA molecules, can induce generation of tumor specific T cells, further generates immune response of targeting tumor cells, can be used as a target spot for clinical treatment or diagnosis of tumors, and has a good application prospect in tumor immunotherapy. The method for separating and screening the tumor neoantigen polypeptide provided by the invention solves the problem that the neoantigen of a non-surgical treatment patient cannot be obtained by the existing method, and provides an effective method for developing the tumor neoantigen polypeptide.

The invention provides a method for changing a cell strain HLA (human leukocyte antigen) to present peptide, a cell strain with changed HLA to present peptide and application of the cell strain. The method for changing the cell strain HLA to present peptide comprises the following steps. The HLA gene is transduced to a K562 cell strain by lentivirus, so that the cell strain expresses an HLA molecule. Then, the cell strain expressing the HLA molecules is transduced by lentivirus with the AIRE gene, and a gene transcription map and a protein map expressed by the cell strain are changed through the over-expressed AIRE effect, so that the variety of peptides presented by the HLA molecules is changed.

The present application relates to the technical field of tumor immunotherapy, and particularly relates to HLA-A*11:01 restricted neoantigen peptides based on malignant pleural effusion tumor cells and application thereof. The present application obtains tumor neoantigen polypeptides by separating and screening from malignant pleural effusion of lung cancer patients, the amino acid sequence of the neoantigen polypeptides is shown in any one of SEQ ID NO. 1-9; the tumor neoantigen polypeptides have high affinity with HLA molecules, can stimulate tumor-specific T cells, and can be used as a target for tumor clinical treatment or diagnosis. The present application further provides a method for separating and screening tumor neoantigen polypeptides, which solves the problem that the neoantigen of non-surgical treatment patients cannot be obtained, and provides an effective method for development of tumor neoantigen polypeptides.

The present application relates to the technical field of tumor immunotherapy, and particularly relates to a tumor neoantigen polypeptide and a method for isolating and screening the same. The amino acid sequence of the tumor neoantigen polypeptide is shown in SEQ ID NO. 1, 2, 3 or 4. The tumor neoantigen polypeptide has high affinity with HLA molecules, can induce tumor-specific T cells, and further produce an immune response targeting tumor cells. The tumor neoantigen polypeptide can be used as a target for tumor clinical treatment or diagnosis, and has good application prospect in tumor immunotherapy. The method for isolating and screening the tumor neoantigen polypeptide provided by the present application solves the problem that the existing method cannot obtain neoantigens of patients who are not treated by surgery, and provides an effective method for developing tumor neoantigen polypeptides.

The invention provides a method for changing an HLA presentation of peptides in a cell line, a cell line with a changed HLA presentation of peptides and a use thereof. The method for changing the HLA presentation includes following steps. HLA genes are lentiviral-transduced into K562 cell lines, so that the cell lines express HLA molecules. Afterwards, the cell lines expressing the HLA molecule are transduced with a lentiviral vector carrying an AIRE gene. Through the overexpression of AIRE, a gene transcription profile and a protein profile expressed by the cell line are changed, resulting in a change in a type of peptide presented by the HLA molecule.

The present application relates to the technical field of tumor immunotherapy, and particularly relates to HLA-restricted neoantigen polypeptides based on malignant ascites tumor cells and application thereof. The present application provides cholangiocarcinoma neoantigen polypeptides, and the amino acid sequence of the neoantigen polypeptides is shown as SEQ ID NO. 1, 2 or 3. The present application obtains tumor neoantigen polypeptides from cholangiocarcinoma patient malignant ascites through separation and screening, the neoantigen polypeptides have high affinity with HLA molecules, can stimulate tumor-specific T cells, and further generate immune response targeting tumor cells, and can be used as a target for tumor clinical treatment or diagnosis, and has good application prospect in tumor immunotherapy.

The present disclosure is directed to methods of modifying an HLA-binding pocket in an HLA molecule in a subject. Some aspects are directed to HLA molecules comprising a modified HLA-binding pocket, where the HLA molecule has increased affinity for a peptide, e.g., an antigen. Other aspects are directed to compositions comprising the same and methods of using the same.

The present application relates to the technical field of tumor immunotherapy, and particularly relates to HLA-restricted neoantigen polypeptide based on malignant ascites tumor cells and application thereof. The present application provides a cholangiocarcinoma neoantigen polypeptide, and an amino acid sequence of the neoantigen polypeptide is shown as SEQ ID NO. 3. The present application obtains a tumor neoantigen polypeptide by separating and screening from malignant ascites of a cholangiocarcinoma patient, the neoantigen polypeptide has high affinity with HLA molecules, can stimulate tumor-specific T cells to produce, and further produce an immune response targeting tumor cells, and can be used as a target point for clinical treatment or diagnosis of tumors, and has a good application prospect in tumor immunotherapy.

The application belongs to the technical field of immunobiology, and particularly relates to a Ewing's sarcoma antigen peptide and application thereof. The Ewing's sarcoma antigen peptide provided by the application is based on the etiological gene fusion mutation of Ewing's sarcoma, high-frequency fusion gene mutations in the human population are detected by using second-generation sequencing data, and the optimal Ewing's sarcoma antigen peptide obtained by further analysis and prediction. The Ewing's sarcoma antigen peptide is a fusion gene neoantigen, the overlap rate of the Ewing's sarcoma antigen peptide with patients can be as high as 100%, and the Ewing's sarcoma antigen peptide not only has high bioinformatics frequency, but also has high affinity with HLA molecules, and has the potential of specific recognition of tumor cells. In addition, it is verified by immunogenicity experiments that the Ewing's sarcoma antigen peptide has good immunogenicity and immunoprotective power, and the Ewing's sarcoma antigen peptide has great market value for the development of a vaccine for preventing and / or treating Ewing's sarcoma.

The present invention relates to the field of biotechnology, and specifically, to a chimeric antigen receptor targeting non-classical HLA molecules for cancer treatment, its modified immune cells, preparation methods and applications. The chimeric antigen receptor specifically targeting HLA-G provided by the present invention has an extracellular domain that is the antigen binding domain of the ILT4 receptor. Compared with CAR-modified immune cells with the antigen binding region of an antibody as the extracellular region, the HLA-G targeted immune response cells provided by the present invention can, on the one hand, broadly identify numerous tumor cells, greatly improving the killing efficiency and accuracy of various types of tumor cells; on the other hand, the extracellular domain is the antigen binding domain of the ILT4 receptor, which is the binding domain of a natural receptor. Compared with artificially synthesized antibodies, it is safe and reliable and can truly reflect the target binding ability in the natural state.

The invention belongs to the technical field of immunobiology, and particularly relates to an Ewing's sarcoma antigen peptide and application thereof. The Ewing's sarcoma antigen peptide provided by the invention is an optimal Ewing's sarcoma antigen peptide obtained by detecting high-frequency fusion gene mutation in people by utilizing next-generation sequencing data on the basis of Ewing's sarcoma pathogenesis-gene fusion mutation and further analyzing and predicting. The Ewing's sarcoma antigen peptide is a fusion gene new antigen, the overlapping rate of the Ewing's sarcoma antigen peptide and a patient can reach up to 100%, and meanwhile, the Ewing's sarcoma antigen peptide not only has bioinformatics high frequency, but also has high affinity with HLA molecules, and has the potential of specifically recognizing tumor cells. Besides, an immunogenicity experiment verifies that the Ewing's sarcoma antigen peptide has good immunogenicity and immune protection capacity, and the Ewing's sarcoma antigen peptide has great market value when being used for preparing vaccines for preventing and / or treating Ewing's sarcoma.

This invention relates to the field of tumor immunotherapy technology, and more particularly to HLA-restricted neoantigen peptides based on malignant ascites tumor cells and their applications. This invention provides a cholangiocarcinoma neoantigen peptide, the amino acid sequence of which is shown in SEQ ID NO.3. This invention isolates and screens tumor neoantigen peptides from malignant ascites of cholangiocarcinoma patients. These neoantigen peptides have a high affinity for HLA molecules, can stimulate the production of tumor-specific T cells, and thus generate an immune response targeting tumor cells. They can serve as targets for clinical treatment or diagnosis of tumors and have promising applications in tumor immunotherapy.

This invention relates to the field of tumor immunotherapy technology, and more particularly to HLA-restricted neoantigen peptides based on malignant ascites tumor cells and their applications. This invention provides a cholangiocarcinoma neoantigen peptide, the amino acid sequence of which is shown in SEQ ID NO.2. This invention isolates and screens tumor neoantigen peptides from malignant ascites of cholangiocarcinoma patients. These neoantigen peptides have a high affinity for HLA molecules, can stimulate the production of tumor-specific T cells, and thus generate an immune response targeting tumor cells. They can serve as targets for clinical treatment or diagnosis of tumors and have promising applications in tumor immunotherapy.

The present disclosure provides modified HLA molecules, and methods of using the same to induce or enhance cytotoxicity, the molecules comprising an alpha chain and a beta chain, wherein both chains comprise one or more substituted cysteines that pair to form disulfide bonds, and wherein the modified HLA molecules are optionally further conjugated to an Fc domain at the 3' end.